Humoral immune response to hepatitis C after liver transplantation: Assessment of a new recombinant immunoblot assay

OBJECTIVE: The immune control of infection with hepatitis C virus (HCV) is poorly understood; vigorous antibody responses to viral proteins seem to co exist with the virus and thus whether they are neutralizing remains controv ersial. HCV-related liver failure is the leading indication for orthotopic liver transplantation (OLT) worldwide. Attenuated antibody responses in imm unosuppressed patients and decreased reliability compared to assessment of HCV RNA has hampered the use of antibody testing post-OLT. The goals of thi s current analysis were twofold: to determine the sensitivity of a prototyp e strip immunoblot assay (RIBA 3.0, Chiron Diagnostics) for the diagnosis o f HCV post-OLT; to determine if there was a correlation between antibody re sponse and severity of histological recurrence. METHODS: The study was comprised of 76 HCV-positive individuals divided int o three patient groups: liver allograft recipients with evidence of mild or no histological recurrence (n = 52), liver allograft recipients with evide nce of severe HCV recurrence and allograft cirrhosis (n = 12), and nontrans plant patients being enrolled in an induction interferon trial (n = 12). Al l transplant patients had histological follow-up of at least 1 yr. RESULTS: Sixty of the 64 (94%) HCV-positive OLT recipients had ii reactivit y to two or more recombinant antigens; three of the patients who lacked a d etectable response had minimal histological recurrence and one had severe r ecurrence. All nontransplant patients demonstrated 4+ reactivity to at leas t two antigens, and 55/64 (86%) OLT recipients demonstrated this same level of reactivity. Seven of the nine patients lacking this high level of react ivity had evidence of minimal recurrence. Furthermore, the mean (+/- SEM) l evel of antibody reactivity for c100 (p = 0.04) and NS5 (p = 0.01) were sig nificantly tower for patients with mild recurrence after OLT, compared to t he other groups. The level of antibody reactivity was unrelated to HCV geno type or viral load. CONCLUSIONS: The recently developed RIBA 3.0 assay for detection of antibod ies to HCV appears to be highly sensitive for the diagnosis of HCV post-OLT . In general, the level of antibody reactivity was comparable in the transp lant patients and in nonimmunosuppressed controls. The pathogenic implicati ons of the relatively diminished humoral response in patients with mild rec urrence post-OLT are discussed. (C) 2000 by Am. Cell. of Gastroenterology.